Pyridazine amine compounds, in particular pyridazine amine compounds with an amino group in the 4-position of the pyridazine moiety, are versatile intermediate compounds for the preparation of pyridazine derived fine chemicals, such as compounds in the pharmaceutical and agrochemical field. For example, pyridazine amine compounds are in the focus of research for pharmaceuticals, which are e.g. suitable for the treatment of Alzheimer dementia, depression, hypotension, and anxiety. Furthermore, pyridazine amine compounds are versatile intermediate compounds for the preparation of pesticides with a pyridazine moiety, such as 4-pyrazole-N-pyridazineamide compounds, which are known to be particularly useful for combating invertebrate pests (see WO 2009/027393, WO 2010/034737, WO 2010/034738, and WO 2010/112177).
For certain applications, pyridazine amine compounds are desired, which do not comprise any further substituents apart from the amino substituent, especially pyridazine amine compounds, which are not further substituted by halogen substituents, e.g. chlorine. However, chlorine substituents are often present in pyridazine amine compounds, as the typical starting material for the preparation of these compounds by means of a nucleophilic substitution reaction with an amine compound is 3,4,5-trichloropyridazine.
In view of the above, there is a need for an effective dehalogenation process, by which dichloropyridazine amine compounds can be converted into pyridazine amine compounds. In particular, there is a need for a process, which provides improved yields. In view of subsequent transformations of the resulting pyridazine amines, it is further desired to perform the reaction without the addition of water.
It is known in the art that dehalogenation of certain dichloropyridazine amine compounds can be performed by a hydrogenation/dehalogenation reaction in the presence of hydrogen and a hydrogenation catalyst. The art suggests that this hydrogenation/dehalogenation of pyridazine amine compounds is performed in the presence of a base. In this regard, reference is made to WO 2011/038572; Journal of Heterocyclic Chemistry, 21(5), 1389-92; 1984; WO 2009/152325; U.S. Pat. No. 4,728,355; WO 2011/124524; WO 2010/049841; WO 2013/142269; U.S. Pat. No. 6,258,822; and WO 2001/007436. For example, WO 2011/038572 discloses the dehalogenation of a mixture of 3,5-dichloro-4-pyridazineamine and 5,6-dichloro-4-pyridazineamine by reacting the mixture with hydrogen in the presence of a hydrogenation catalyst (Pd/C) and a base (sodium hydroxide).
The reason why the base is added is to avoid catalyst poisoning due to the production of HCl in the reaction. This is explained by F. Chang et al. in Bull. Korean Chem. Soc. 2011, 32(3), 1075, an article that relates to Pd-catalyzed dehalogenations of aromatic halides. It is disclosed that HCl produced from dechlorination tends to be absorbed on the activated carbon, leading to a progressive poisoning of Pd/C, and that it is efficient to add some bases for the removal of HCl. It is further disclosed that the conversions in the dechlorination reaction can be increased in the presence of a base.
However, the addition of a base is disadvantageous, in particular for an industrially applicable process. First, an additional chemical substance is required for the reaction, i.e. the base, which makes the process more complex. Second, the presence of the base makes catalyst recycling difficult. In particular, when filtering off the hydrogenation catalyst after the reaction, chloride salts obtained from the reaction of the base with the HCl will additionally be filtered off, so that the filter cake comprises both, the catalyst and the chloride salt (e.g. KCl and KHCO3). A further work-up procedure is then required to isolate the catalyst again.